This invention relates to diffusion imaging of tissues.
In the past decade, magnetic resonance imaging (MRI) methods have been developed that by mapping the diffusion tensor of tissue water can nondestructively map the structural anisotropy of fibrous tissues in living systems. Recently, these methods have been used to elucidate fiber architecture and functional dynamics of the myocardium and of skeletal muscle, and used in the nervous system to identify and map the trajectories of neural white matter tracts and infer neuroanatomic connectivity.
Notwithstanding this progress, the diffusion tensor paradigm has limitations. Because MRI spatial resolution typically is far in excess of the diffusion scale, each resolution element (voxel) represents the summed signal of distinct diffusional environments, which is generally under-specified by the six degrees of freedom of the diffusion tensor.
The invention relates to the use of diffusion spectrum MRI to map complex fiber architectures or structures in tissues with a high level of resolution. The new methods resolve intravoxel heterogeneity of diffusion in vivo with MRI of diffusion density spectra.
In general, the invention features a method of constructing an image representative of structure within a tissue, by (a) inducing a population of spins in the tissue to produce a set of nuclear magnetic resonance (NMR) signals, wherein the set comprises a family of complex Fourier-encodings of a distribution of three-dimensional displacements of the spins in the population; (b) converting each of the NMR signals in the family of complex Fourier-encodings into a positive number to form a family of positive numbers; (c) reconstructing from the family of positive numbers a function that approximates the distribution of three-dimensional displacements of the spins in the population; and (d) constructing an image that represents the function, whereby the image represents structure within the tissue.
In this method, each spin in the population can be within a three-dimensional voxel, and the population of spins can be induced to produce the set of NMR signals by the application of a set of magnetic gradient pulses, e.g., applied in a pulse train whose time-intensity integral is zero. The pulses in the pulse train can be bipolar gradient pulses, and the gradient pulses can be transected by one or more 180xc2x0 radio frequency (RF) pulses and the gradient sign can be reversed following each 180xc2x0 pulse. The NMR signals can also be converted into positive numbers by determining the modulus (z- greater than |z|), or by determining the squared modulus (z- greater than zz*).
In the new methods, the function can reconstructed by determining the discrete Fourier transform, or by interpolation and regridding, followed by determining the discrete Fourier transform. In some embodiments, the new methods can be performed for multiple contiguous locations in the tissue, and then followed by further constructing a curve that represents fiber tracts in the tissue that conform to the orientation of directions of maximum displacement.
In some embodiments, the image is a three-dimensional graphic image, e.g., that represents the three-dimensional distribution of spin displacement for a voxel. The graphic image can also be a three-dimensional polar plot of the amplitude of spin displacement in multiple directions, and the polar plot can be colored to represent the amplitude and orientation of spin displacement. For example, the color can be coded to assign red, green, and blue to the amplitude of spin displacement in each of three orthogonal coordinates. The amplitude of spin displacement is the relative probability of spins displacing a constant distance in any direction.
The graphic image can also be a density plot of the spin density in a position-angle space, e.g., a slice or projection through a 6-dimenional position-angle space.
In these methods the tissue is a heterogeneous tissue, e.g., a tissue with two or more tissue types. The tissue can be brain tissue, e.g., neural white matter, that may have, for example, multiple fiber orientations. The tissue can also comprise normal and pathologic tissue, and the pathologic tissue can be cerebral edema, cerebral hematoma, cerebral neoplasm, cerebral metastasis, or ischemic tissue. The pathologic tissue can also comprise a neurodegenerative disease, such as Huntington""s chorea, multiple sclerosis, or stroke. The tissue can also be muscle, such as heart or tongue.
In another embodiment, the new methods can be used to diagnose a disorder in a tissue, such as brain or heart using the image. In other embodiments, the methods can be used to construct a model of fiber tracts in the brain based on the image or to map a surgical site in the tissue, e.g., the brain or heart, using the image. The image can be combined with images of other magnetic resonance imaging (MRI) contrast parameters, such as NMR contrast parameters, e.g., T1, T2, magnetization transfer contrast (MTC), or blood oxygen level dependent contrast (BOLD).
In yet another embodiment, the invention includes a computer-implemented program for constructing an image representative of structure within a tissue, the program comprising a plurality of program instructions stored on a electronic apparatus-readable medium for implementing the steps of: (a) inducing a population of spins in the tissue to produce a set of nuclear magnetic resonance (NMR) signals, wherein the set comprises a family of complex Fourier-encodings of a distribution of three-dimensional displacements of the spins in the population; (b) converting each of the NMR signals in the family of complex Fourier-encodings into a positive number to form a family of positive numbers; (c) reconstructing from the family of positive numbers a function that approximates the distribution of three-dimensional displacements of the spins in the population; and (d) constructing an image that represents the function, whereby the image represents structure within the tissue.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description, and from the claims.